Navegando por Autor "Martins, Felipe Terra"

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2,2’,4-Trihydroxybenzophenone : crystal structure, and anti-inflammatory and antioxidant activities.
(2007) Doriguetto, Antônio Carlos; Martins, Felipe Terra; Ellena, Javier Alcides; Salloum, Rogério; Santos, Marcelo Henrique dos; Moreira, Maria Eliza de Castro; Silva, Jose Mauricio Schneedorf Ferreira da; Nagem, Tanus Jorge
The crystal structure of C 2,2’,4-trihydroxybenzophenoneD (¼(2,4-dihydroxyphenyl)(2-hydroxyphenyl) methanone; 1) was determined, and its molecular structure, along with intra- and intermolecular Hbonds, was analyzed. The anti-inflammatory potential of 1, evaluated by means of the rat-paw-edema assay, with carrageenan as inflammation stimulus, was found to be similar high as that of indomethacin. In contrast, benzophenone proper (2) was hardly active in this assay. Our results indicate that these antiinflammatory effects are related to the action of kinins and prostaglandins. The radical-scavenging properties of 1 towards DPPH were found to be similar as those of typical phenolics, but somewhat lower than that of ascorbic acid. The structure–activity relationship (SAR) of 1 is discussed.
Antiproliferative effect of benzophenones and their infl uence on cathepsin activity.
(2010) Murata, Ramiro Mendonça; Yatsuda, Regiane; Santos, Marcelo Henrique dos; Kohn, Luciana K.; Martins, Felipe Terra; Nagem, Tanus Jorge; Alencar, Severino Matias de; Carvalho, João Ernesto de; Rosalen, Pedro Luiz
The antiproliferative activity of two prenylated benzophenones isolated from Rheedia brasiliensis, the triprenylated garciniaphenone and the tetraprenylated benzophenone 7-epiclusianone, was investigated against human cancer cell lines. The antiproliferative activity on melanoma (UACC-62), breast (MCF-7), drug-resistant breast (NCI-ADR), lung/non-small cells (NCI460), ovarian (OVCAR 03), prostate (PC03), kidney (786-0), lung (NCI-460) and tongue (CRL-1624 and CRL-1623) cancer cells was determined using spectrophotometric quantifi cation of the cellular protein content. The effect of these benzophenones on the activity of cathepsins B and G was also investigated. Garciniaphenone displayed cytostatic activity in all cell lines, whereas 7- epiclusianone showed a dose-dependent cytotoxic effect. The IC50 values for cell proliferation revealed that 7-epiclusianone is more active than garciniaphenone against most of the cell lines. Furthermore, the antiproliferative effects demonstrated by garciniaphenone and 7-epiclusianone were related to their cathepsin inhibiting properties. In conclusion, 7-epiclusianone is a promising naturally occurring agent which displays multiple inhibitory effects which may be working in concert to inhibit cancer cell proliferation in vitro. The putative pathway by which 7-epiclusianone affects cancer cell development may involve cathepsin inhibition.
Conformerism, enantiomorphism and double catemer motifs in para-substituted nostoclide analogues.
(2016) Teixeira, Róbson Ricardo; Barbosa, Luiz Cláudio de Almeida; Antolinez, Isabel Valero; Correa, Rodrigo de Souza; Martins, Felipe Terra; Doriguetto, Antônio Carlos
Evaluation of anti-candida albicans activity and release of ketoconazole in PMMA-G-PEG 4000 films.
(2022) Reynaldo, Juliana Ribeiro; Novack, Kátia Monteiro; Sousa, Lucas Resende Dutra; Vieira, Paula Melo de Abreu; Amparo, Tatiane Roquete; Souza, Gustavo Henrique Bianco de; Teixeira, Luiz Fernando de Medeiros; Barboza, Ana Paula Moreira; Neves, Bernardo Ruegger Almeida; Alvarenga, Meiry Edivirges; Martins, Felipe Terra; Santos, Viviane Martins Rebello dos
Modified release systems depend on the selection of an appropriate agent capable of controlling the release of the drug, sustaining the therapeutic action over time, and/or releasing the drug at the level of a particular tissue or target organ. Polyethylene glycol 4000 (PEG 4000) is commonly employed in drug release formulations while polymethyl methacrylate (PMMA) is non-toxic and has a good solubility in organic solvents. This study aimed at the incorporation of ketoconazole in PMMA-g-PEG 4000 and its derivatives, thus evaluating its release profile and anti-Candida albicans and cytotoxic activities. Ketoconazole was characterized and incorporated into the copolymers. The ketoconazole incorporated in the copolymer and its derivatives showed an immediate release profile. All copolymers with ketoconazole showed activity against Candida albicans and were non-toxic to human cells in the entire concentration tested.
New multicomponent crystal forms of adiphenine with low hygroscopicity.
(2022) Ribeiro, Thiago; Silva, Alisson Moraes e; Araujo Neto, João Honorato de; Viana, André Luis Machado; Faria, Henrique Dipe de; Ruela, André Luís Morais; Doriguetto, Antônio Carlos; Oliveira, Cecilia Maria Alves; Martins, Felipe Terra
Adiphenine is an acetylcholine receptor inhibitor used as an antispasmodic drug due to its strong smooth muscle relaxant action. Adiphenine hydrochloride is largely marketed in drug associations to treat muscle spasms and relieve pain in colic and cramps. However, it presents serious problems with hygroscopicity and chemical stability under high humidity conditions, which have limited its use as an active pharmaceutical ingredient (API). Here, we have solved the adiphenine solid-state hygroscopicity problem through the preparation of stable, nonhygroscopic multicomponent crystal forms thereof. Two new salts of adiphenine were designed by recognition of intermolecular interaction patterns in the Cambridge Structural Database (CSD) and ΔpKa rules. Two generically recognized as safe (GRAS) coformers, namely, citric acid and oxalic acid, were chosen and formed monobasic salts with adiphenine. Crystal structure elucidation reveals that adiphenine adopts different conformations in our salts, while in the literature, hydrochloride adopts one, which is related to different intermolecular arrays. In the dynamic vapor sorption (DVS) analysis, it was verified that adiphenine citrate and adiphenine oxalate starts to incorporate water slowly from 50 to 70% of relative humidity (RH), increasing up to 3.2 and 2.6% of their initial masses in 90% of RH, respectively. At the end of the desorption cycle (RH = 0%), the samples retained only 0.12 and 0.08% of water relative to their initial masses. On the other hand, adiphenine hydrochloride exhibits a classical high hygroscopicity behavior, which retains water fast from 50% of relative humidity (RH), increasing up to 22% of its initial mass in 90% of RH and a net mass gain of 5% at the end of the desorption cycle (RH = 0%). Notably, both carboxylic acid salts had similar solubility as a function of medium pH, while the hydrochloride one was more soluble than them by factors ranging from 6.7 (relative to citrate in pH 1.2) to 28.2 (relative to oxalate in pH 4.5). Nevertheless, the pharmacokinetic parameters of adiphenine after oral administration of the capsules containing the salt forms did not reflect these solubility differences, since all adiphenine salt forms can be considered highly soluble drugs according to the Biopharmaceutics Classification System (dose/solubility ratio < 250 mL). It was observed that the rats treated with capsules containing adiphenine hydrochloride had an increase in AUC0−∞ (1537 vs 914 vs 991 min μg mL−1 ) compared with rats treated with adiphenine citrate and oxalate capsules, respectively, even though the same tmax (48 min) was observed. However, dosage tuning can bring the bioavailability of our salts into that of the hydrochloride salt, with the advantage of nonhygroscopicity and higher chemical stability.
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells.
(2019) Oliveira, Maiara de Souza; Barbosa, Marília Imaculada Frazão; Souza, Thiago Belarmino de; Moreira, Diogo Rodrigo de Magalhães; Martins, Felipe Terra; Villarreal, Wilmer; Machado, Rafael Pereira; Doriguetto, Antônio Carlos; Soares, Milena Botelho Pereira; Bezerra, Daniel Pereira
Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became a novel potential antineoplastic agent. In the present study, we synthesized a novel platinum complex containing a piplartine derivative cis-[PtCl(PIP-OH)(PPh3)2]PF6 (where, PIP-OH = piplartine demethylated derivative; and PPh3 = triphenylphosphine) with enhanced cytotoxicity in different cancer cells, and investigated its apoptotic action in human promyelocytic leukemia HL-60 cells. The structure of PIP-OH ligand was characterized by X-ray crystallographic analysis and the resulting platinum complex was characterized by infrared, molar conductance measurements, elemental analysis and NMR experiments. We found that the complex is more potent than piplartine in a panel of cancer cell lines. Apoptotic cell morphology, increased internucleosomal DNA fragmentation, without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization and caspase-3 activation were observed in complex-treated HL-60 cells. Treatment with the complex also caused a marked increase in the production of reactive oxygen species (ROS), and the pretreatment with N-acetyl-L-cysteine, an antioxidant, reduced the complex-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. Important, pretreatment with a p38 MAPK inhibitor (PD 169316) and MEK inhibitor (U-0126), known to inhibit ERK1/2 activation, also prevented the complex-induced apoptosis. The complex did not induce DNA intercalation in cell-free DNA assays. In conclusion, the complex exhibits more potent cytotoxicity than piplartine in a panel of different cancer cells and triggers ROS/ERK/p38-mediated apoptosis in HL-60 cells.